Single-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells

Atherosclerosis is a lipid-driven chronic inflammatory disease; however, whether it can be classified as an autoimmune disease remains unclear. In this study, we applied single-cell T cell receptor seqencing (scTCR-seq) on human carotid artery plaques and matched peripheral blood mononuclear cell sa...

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Published in:Nature Cardiovascular Research Vol. 2; no. 2; pp. 112 - 125
Main Authors: Depuydt, Marie A. C., Schaftenaar, Frank H., Prange, Koen H. M., Boltjes, Arjan, Hemme, Esmeralda, Delfos, Lucie, de Mol, Jill, de Jong, Maaike J. M., Bernabé Kleijn, Mireia N. A., Peeters, Judith A. H. M., Goncalves, Lauren, Wezel, Anouk, Smeets, Harm J., de Borst, Gert J., Foks, Amanda C., Pasterkamp, Gerard, de Winther, Menno P. J., Kuiper, Johan, Bot, Ilze, Slütter, Bram
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.02.2023
Nature Publishing Group UK
Subjects:
Antigens
Atherosclerosis
Cytomegalovirus
Flow cytometry
Genomics
Leukocytes
Lymphocytes
Patients
Protein expression
Proteins
T cell receptors
Autoimmunity
Atherosclerosis
ISSN:2731-0590, 2731-0590
Online Access:Get full text
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Summary:Atherosclerosis is a lipid-driven chronic inflammatory disease; however, whether it can be classified as an autoimmune disease remains unclear. In this study, we applied single-cell T cell receptor seqencing (scTCR-seq) on human carotid artery plaques and matched peripheral blood mononuclear cell samples to assess the extent of TCR clonality and antigen-specific activation within the various T cell subsets. We observed the highest degree of plaque-specific clonal expansion in effector CD4 + T cells, and these clonally expanded T cells expressed genes such as CD69 , FOS and FOSB , indicative of recent TCR engagement, suggesting antigen-specific stimulation. CellChat analysis suggested multiple potential interactions of these effector CD4 + T cells with foam cells. Finally, we integrated a published scTCR-seq dataset of the autoimmune disease psoriatic arthritis, and we report various commonalities between the two diseases. In conclusion, our data suggest that atherosclerosis has an autoimmune compondent driven by autoreactive CD4 + T cells.
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ISSN:2731-0590
2731-0590
DOI:10.1038/s44161-022-00208-4